The strong association between depression and antiretroviral (ARV) nonadherence, together with the high prevalence of depression in HIV, suggests the need for interventions targeting depressed patients with adherence problems. Antidepressant therapy has been proven to be an effective treatment for depression, but whether it is sufficient to significantly improve and sustain ARV adherence is unknown. Are adjunctive strategies to mental health treatment, that specifically target pill taking behavior, needed to enable depressed patients to achieve and sustain high adherence? The proposed pilot is a randomized controlled trial comparing the combination of antidepressants plus cognitive-behavioral training versus antidepressant therapy alone in improving ARV adherence among 70 depressed HIV patients with demonstrated adherence problems. The primary goals of the pilot are to determine estimates of critical design parameters for informing a subsequent larger trial and R01 application, including rates of enrollment and attrition, and magnitude of effect on antiretroviral adherence. The cognitive-behavioral training component will be based on principles of cognitive-behavioral therapy and the IMB model of health behavior, and will consist of 5 individual core sessions (Weeks 00,1, 2, 4, 8) plus one maintenance module (beginning at Week 16). Antidepressant therapy will be individualized with selection of antidepressant based on each patient's history with antidepressant therapy and antidepressant side effect profile. Primary assessments are at study baseline and Weeks 16 and 24. If results of this pilot are promising, it will form the basis for an R01 application to conduct a larger controlled trial of the intervention. If the intervention model is shown to be among the field's first to produce a robust and durable effect, it could not only be integrated into standard HIV clinical management and improve the clinical outcomes of this sizeable subpopulation, but also encourage the development and evaluation of other interventions that combine behavioral and pharmacologic components in the context of adherence to chronic medical treatments. This study is important to public health as its findings may guide the development and evaluation of an intervention that may help depressed patients to adhere well to antiretroviral therapy and receive optimal benefit from treatment, including limiting drug resistance and the transmission of multi-drug resistance virus. [unreadable] [unreadable] [unreadable] [unreadable]